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Researchers discover how worms' noses sense oxygen

eplaces oxygen.

The puzzle has been why the heme in guanylate cyclase is able to exclude oxygen from its binding site and reserve it only for NO. This molecular question - the key to understanding how NO works - has been a focus of the Marletta lab, and pursuit of the answer led directly to oxygen sensing in worms.

The discovery of a similar enzyme in the nematode, but one that binds oxygen instead of NO, will help Marletta and his colleagues discover the tricks used by the enzyme to let in or screen out oxygen from the heme binding site to selectively detect one or the other.

"This experiment helps us understand how NO receptors in muscle and brain are able to bind selectively to NO in low concentrations even when oxygen is present in far greater concentrations," he said. "This could have implications across a wide swath of biology, in cases where organisms need to bind NO in low concentrations and very selectively."

In order to understand how guanylate cyclase is put together, Marletta and his students went in search of similar enzymes in the genomes of other organisms. Patricia Pellicena, a UC Berkeley postdoctoral fellow with collaborator John Kuriyan, a UC Berkeley professor of chemistry, found homologues not only in the nematode, but also in more primitive organisms called bacterial prokaryotes. One group of these, the obligate anaerobes, die in the presence of oxygen, so they evidently require a sensitive oxygen detector.

This insight helped graduate students David S. Karow of UC Berkeley and Jesse M. Gray of UCSF make sense of puzzling data they were obtaining about C. elegans' response to NO. Perhaps this enzyme was serving as an oxygen detector, not as a NO detector, in C. elegans?

By manipulating oxygen levels in Petri dishes filled with worms feeding on a lawn of bacteria, the researchers were able to show that bordering and clumping was actually a response to high oxygen levels. Karow and Gray employed a c
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Contact: Robert Sanders
rls@pa.urel.berkeley.edu
510-643-6998
University of California - Berkeley
8-Jul-2004


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